This is an investigation of the effects of interactions between epithelium and stroma during transformation of epithelium from normal to neoplastic state. The systems studied are: 1) Tumors of the submandibular salivary gland of mice, induced by polyoma virus; 2) Mammary tumors of mice, spontaneous or induced by mammary tumor virus (MTV). The methods used involve neoplastic transformation of epithelium in the presence or absence of specific types of mesenchyme (stroma). The results are evaluated on the basis of morphological and biological properties of the resulting neoplasms. Findings are that neoplastic changes induced in salivary epithelium by polyoma virus have widely variable characteristics, depending on whether the transformational and post-transformational events take place in the presence or absence of stromal cells. Stromal cells are not necessary for epithelial cell transformation, but epithelium transformed in a microenvironment devoid of other cellular components gives rise to tumors that are morphologically more atypical and biologically more aggressive than tumors induced either in vivo or in organotypic culture. The evidence suggests that stromal components may act to inhibit or decelerate tumor progression and to influence the type and degree of differentiation expressed by the neoplastic cells.